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Background <p>Direct oral anticoagulants (DOACs) reduce thromboembolism in atrial fibrillation (AF), but their effect on cardiac outcomes is less studied.</p> Methods <p>Systematic review and network meta-analysis were performed on AF patients on DOACs/vitamin K antagonists (VKAs). Both observational studies and randomized clinical trials (RCTs) were included. Endpoints were myocardial infarction (MI) and major adverse cardiac events (MACE). Rankograms and SUCRA were performed. Sub-group analysis included age (&lt;/≥ 75&#xa0;years) and length of follow-up (&lt;/≥ 12&#xa0;months).</p> Results <p>50 studies (3 RCTs, 4 post hoc analyses of RCTs and 43 observational studies) with 1,769,987 patients were included (59.9% on DOACs and 45.3% women).</p> <p>The MI risk (46 studies with 1,554,704 patients) was lower in all DOACs compared to VKA (apixaban: hazard ratio [HR] 0.83, 95% credible interval [95%CI 0.72–0.96], edoxaban: HR 0.68, 95%CI 0.53–0.86, rivaroxaban: HR 0.84, 95%CI 0.74–0.95, dabigatran: HR 0.85, 95%CI 0.75–0.97). SUCRA showed edoxaban as first choice for preventing MI overall. In patients aged &lt; 75&#xa0;years, a lower MI risk was found for edoxaban (HR 0.60, 95%CI 0.41–0.85), while in those aged ≥ 75&#xa0;years, no significant difference was found among anticoagulants. Heterogeneity was low in all analyses. Network meta-analysis showed no differences among DOACs.</p> <p>Compared to VKA, apixaban (HR 0.77, 95%CI 0.63–0.97) was associated with lower MACE risk. Analysis of SUCRA showed apixaban as first choice for preventing MACE overall and in patients treated for &lt; 12&#xa0;months.</p> Conclusion <p>DOACs were associated with a lower risk of MACE/MI in AF. The effect of DOACs on cardiovascular risk differs according to aging and follow-up length. However, our findings are based on indirect evidence, and further studies are needed.</p> PROSPERO registration number <p>CRD42023407778.</p>

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Effects of direct oral anticoagulants on cardiac outcomes in atrial fibrillation: a systematic review and network meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Danilo Menichelli,
  • Daniele Malatesta,
  • Arianna Pannunzio,
  • Alessio Farcomeni,
  • Francesco Violi,
  • Pasquale Pignatelli,
  • Daniele Pastori

摘要

Background

Direct oral anticoagulants (DOACs) reduce thromboembolism in atrial fibrillation (AF), but their effect on cardiac outcomes is less studied.

Methods

Systematic review and network meta-analysis were performed on AF patients on DOACs/vitamin K antagonists (VKAs). Both observational studies and randomized clinical trials (RCTs) were included. Endpoints were myocardial infarction (MI) and major adverse cardiac events (MACE). Rankograms and SUCRA were performed. Sub-group analysis included age (</≥ 75 years) and length of follow-up (</≥ 12 months).

Results

50 studies (3 RCTs, 4 post hoc analyses of RCTs and 43 observational studies) with 1,769,987 patients were included (59.9% on DOACs and 45.3% women).

The MI risk (46 studies with 1,554,704 patients) was lower in all DOACs compared to VKA (apixaban: hazard ratio [HR] 0.83, 95% credible interval [95%CI 0.72–0.96], edoxaban: HR 0.68, 95%CI 0.53–0.86, rivaroxaban: HR 0.84, 95%CI 0.74–0.95, dabigatran: HR 0.85, 95%CI 0.75–0.97). SUCRA showed edoxaban as first choice for preventing MI overall. In patients aged < 75 years, a lower MI risk was found for edoxaban (HR 0.60, 95%CI 0.41–0.85), while in those aged ≥ 75 years, no significant difference was found among anticoagulants. Heterogeneity was low in all analyses. Network meta-analysis showed no differences among DOACs.

Compared to VKA, apixaban (HR 0.77, 95%CI 0.63–0.97) was associated with lower MACE risk. Analysis of SUCRA showed apixaban as first choice for preventing MACE overall and in patients treated for < 12 months.

Conclusion

DOACs were associated with a lower risk of MACE/MI in AF. The effect of DOACs on cardiovascular risk differs according to aging and follow-up length. However, our findings are based on indirect evidence, and further studies are needed.

PROSPERO registration number

CRD42023407778.